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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02550054
Other study ID # CHFudanU_NNICU4
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date September 8, 2015
Est. completion date December 30, 2016

Study information

Verified date December 2023
Source Children's Hospital of Fudan University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The main goal of this trial is to investigate whether early administration of human erythropoietin (EPO) in preterm infants improves neurodevelopmental outcome at 18 months corrected age. This study is designed as randomized, double-masked, placebo controlled multicenter study involving at least 312 patients.


Description:

EPO has been safely used for prevent preterm anemia and recent studies have shown the neuro-protective effect. Our hypothesis is that EPO could prevent preterm brain injury and reduce the rate of premature death and disability from encephalopathy. The aims of this study include: to investigate the safety and efficacy of EPO by using 1000u/kg higher than the dose of anemia treatment (250u/kg); to evaluate the effect of EPO on neurodevelopment in preterm infants; to detect biological and imaging indicators of EPO. Eligible premature infants will be enrolled in this double-blind, placebo-controlled randomized trial from the neonatal neurological intensive care unit (NNICU) at 7 Children's Hospital in 6 provinces of China. Subjects will be enrolled within the first 24 hours of life and randomly assigned to receive Epo or saline vehicle placebo. Standard NICU care will be provided to all subjects. Pharmacokinetic data, serial brain electrophysiologic and imaging exams, circulating inflammatory mediators, biomarkers and complications like polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, hemorrhage, seizure, necrotizing enterocolitis (NEC), persistent ductus arterious (PDA), apnea of prematurity, pulmonary haemorrhage, pulmonary hypertension, Prolonged blood coagulation time, retinopathy of prematurity (ROP), cardiac arrhythmia, major venous thrombosis, Renal failure treated with dialysis, pneumonia, pulmonary airleak and chronic lung disease will be collected at established time points during the study period. At 18 months corrected age, subjects will undergo a neurodevelopmental evaluation assessing for cerebral palsy, Bayley Scores of Mental Development Index (MDI) use.


Other known NCT identifiers
  • NCT02601872

Recruitment information / eligibility

Status Terminated
Enrollment 58
Est. completion date December 30, 2016
Est. primary completion date December 30, 2016
Accepts healthy volunteers No
Gender All
Age group N/A to 48 Hours
Eligibility Inclusion Criteria: 1. Birthweight less or equal 1500 grams 2. Less than 32 weeks gestation at birth 3. Less than 48 hours of life at time of enrollment 4. Written informed consent of parent or guardian Exclusion Criteria: 1. Intrauterine Growth Retardation 2. Severe Congenital Anomalies adversely affecting life expectancy or neurodevelopment 3. Genetic Metabolic Diseases 4. Seizures within first 24 hours of life 5. Severe neutropenia (ANC < 500 cells/microL) within first 24 hours of life 6. Polycythemia (Hct > 65%) within first 24 hours of life 7. Thrombocytopenia (platelets < 50K cells/microL) within first 24 hours of life 8. Hypertension (SBP > 100mmHg) without vasopressor support within first 24 hours of life 9. Microcephaly 10. Grade III-IV intracranial hemorrhage Termination 1. Required by parent or guardian; 2. Polycythemia through blood transfusion can not be relieved 3. Oliguria(<0.5mL/kg/h for at least 24 hours) 4. Progression of azotemia 5. Pulmonary hypertension or Cardiac arrhythmia

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Epo
Epo is administered 1000 U/kg, iv in 48 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, subcutaneously 400 U/Kg per injection and 3 doses per week until at corrected age of 34 weeks.
Normal saline
Normal saline is administered 5ml, iv at 3 to 6 hours after premature birth, and at 48 hours interval for 3 doses per week. After 6 doses, Subcutaneously 3 doses per week until at corrected age of 34 weeks.

Locations

Country Name City State
China Children Hospital of Fudan University Shanghai Shanghai

Sponsors (7)

Lead Sponsor Collaborator
Children's Hospital of Fudan University Guangzhou Women and Children's Medical Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Maternal and Child Health Hospital of Hubei Province, Second Affiliated Hospital of Wenzhou Medical University, The Maternal & Children Health Hospital of Dehong, Yunnan of China, Xiamen Children's Hospital, Fujian of China

Country where clinical trial is conducted

China, 

References & Publications (4)

Dame C, Langer J, Koller BM, Fauchere JC, Bucher HU. Urinary erythropoietin concentrations after early short-term infusion of high-dose recombinant epo for neuroprotection in preterm neonates. Neonatology. 2012;102(3):172-7. doi: 10.1159/000339283. Epub 2012 Jul 4. — View Citation

Kuki I, Kawawaki H, Horino A, Inoue T, Nukui M, Okazaki S, Tomiwa K, Amo K, Togawa M, Shiomi M. [A clinical study on high-dose erythropoietin therapy for acute encephalopathy or encephalitis]. No To Hattatsu. 2015 Jan;47(1):32-6. Japanese. — View Citation

Leuchter RH, Gui L, Poncet A, Hagmann C, Lodygensky GA, Martin E, Koller B, Darque A, Bucher HU, Huppi PS. Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA. 2014 Aug 27;312(8):817-24. doi: 10.1001/jama.2014.9645. — View Citation

Traudt CM, McPherson RJ, Bauer LA, Richards TL, Burbacher TM, McAdams RM, Juul SE. Concurrent erythropoietin and hypothermia treatment improve outcomes in a term nonhuman primate model of perinatal asphyxia. Dev Neurosci. 2013;35(6):491-503. doi: 10.1159/000355460. Epub 2013 Nov 1. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Neurodevelopment(Bayley Scores) To evaluate neurodevelopmental function via Bayley Scores of Infant Development Mental Development Index (BSID) and gain incidence of MDI<70(Severe) or MDI<85(Moderate). At corrected age of 18 months
Primary Neurological Evaluation(GMFM-88 Scores) To gain changes in standardized gross motor function using GMFM (Gross Motor Function Measure) as a standardized measurement tool for assessing Gross Motor Function consisting of sub-scales, lying & rolling, sitting, crawling & kneeling, standing, walking, running & jumping (range: 0~100 , Higher value means better gross motor function). At corrected age of 18 months
Secondary Brain Structural Alterations(MRI) To compare changes in brain as measured by MRI in Epo treatment and control groups at 9 months. At corrected age of 9 months
Secondary Brain Structural Alterations(MRI) To compare changes in brain as measured by MRI in Epo treatment and control groups at 18 months. At corrected age of 18 months
Secondary Intracranial Hemorrhage(MRI) To compare changes in brain as measured by MRI in Epo treatment and control groups at 9 months. At corrected age of 9 months
Secondary Intracranial Hemorrhage(MRI) To compare changes in brain as measured by MRI in Epo treatment and control groups at 18 months. At corrected age of 18 months
Secondary Brain Parenchyma Alterations(MRI) To compare changes in brain as measured by MRI in Epo treatment and control groups at 9 months. At corrected age of 9 months
Secondary Brain Parenchyma Alterations(MRI) To compare changes in brain as measured by MRI in Epo treatment and control groups at 18 months. At corrected age of 18 months
Secondary Somatosensory Evoked Potential To compare changes in brain electrophysiology by SSEP at 36 weeks. At corrected age of 9 months
Secondary Somatosensory Evoked Potential To compare changes in brain electrophysiology by SSEP at 18 months. At corrected age of 18 months
Secondary Visual Evoked Potential To compare changes in brain electrophysiology by VEP at 36 weeks. At corrected age of 9 months
Secondary Visual Evoked Potential To compare changes in brain electrophysiology by VEP at 18 months. At corrected age of 18 months
Secondary Brain Stem Auditory Evoked Potential To compare changes in brain electrophysiology by BAER at 36 weeks. At corrected age of 9 months
Secondary Brain Stem Auditory Evoked Potential To compare changes in brain electrophysiology by BAER at 18 months. At corrected age of 18 months
Secondary Incidence of complication To gain the incidence of Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, intraventricular hemorrhage(IVH), periventricular leukomalacia(PVL), seizure, necrotizing enterocolitis (NEC), persistent ductus arterious (PDA), apnea of prematurity, pulmonary haemorrhage, pulmonary hypertension, Prolonged blood coagulation time, retinopathy of prematurity(ROP), cardiac arrhythmia, major venous thrombosis, Renal failure treated with dialysis, pneumonia, pulmonary airleak and chronic lung disease. During treament period (in 34 weeks)
Secondary SDF-1 in Serum Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy of erythropoietin for hypoxic ischemic encephalopathy. At 34 weeks
Secondary TNF-alpha in Serum Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy of erythropoietin for hypoxic ischemic encephalopathy. At 34 weeks
Secondary IL-1 in Serum Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy of erythropoietin for hypoxic ischemic encephalopathy. At 34 weeks
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